Pulmonary Arterial Hypertension (PAH) MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Sotatercept
Product Code: ACE-011 / MK-7962
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: SOTATERCEPT
CAS Number: 1001080-50-7
Current Sponsor code: A
Sponsors
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of = 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of = 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes: - Idiopathic PAH - Heritable PAH - Drug-/toxin-induced PAH - PAH associated with CTD - PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair 3. Symptomatic PAH classified as WHO FC II or III 4. Either REVEAL Lite 2 risk score = 6 or COMPERA 2.0 risk score = 2 (intermediate-low-risk or above) 5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening. Background PAH therapy and diuretics are further defined in Section 7.2. 6. 6MWD = 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value). 7. Females of childbearing potential (as defined in Appendix 4) must meet the following criteria: •Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; •Agree to ongoing pregnancy testing (either urine or serum) during the course of the study and until 8 weeks after the last dose of the study drug •If sexually active with a male partner: - Used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, AND - Agreed to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment •Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment 8. Male participants must meet the following criteria: -Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy -Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment 9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements 10. Ability to understand and provide documented written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 164
Exclusion criteria
Exclusion criteria: 1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5 2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease and pulmonary capillary hemangiomatosis. 3. Hgb at screening above gender-specific upper limit of normal (ULN), per local laboratory test 4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest 5. Baseline systolic BP 3 × ULN (For United Kingdom [UK], refer to the specific requirement in Appendix 6) • Platelet count 500 ms during the Screening Period (For UK and South Korea, refer to the specific requirements in Appendix 6). 19. Personal or family history of long QT syndrome or sudden cardiac death 20. .Left ventricular ejection fraction < 50% documented by a historical echocardiograph (ECHO) or cardiac magnetic resonance imaging (MRI) within the last 12 months prior to screening (if there is more than 1 assessment of left ventricular ejection fraction (LVEF), the value from the most recent measurement should be used in assessing eligibility) 21. Coronary artery disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months prior to the Screening Visit 22. Cerebrovascular accident within 3 months prior to the Screening Visit 23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment 24. Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease 25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit 26.Active malignancy with the excepti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the effects of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) on TTCW in participants who are newly diagnosed with PAH and are at intermediate or high risk of PAH disease progression.;Secondary Objective: not applicable;Primary end point(s): The primary efficacy endpoint is TTCW, defined as the time from randomization to the first confirmed morbidity event or death. The events that will comprise this endpoint include the following: • All-cause death • Non-planned PAH-related hospitalization of = 24 hours in duration • Atrial septostomy • Lung transplant • Deterioration in performance in exercise testing due to PAH, defined as a decrease in 6MWD from baseline (average of screening) on 2 consecutive tests (which must be at least 4 hours apart) and at least 1 of the following: - Worsening of WHO FC from baseline - Signs/symptoms of increased right heart failure - Addition of a background PAH therapy or change PAH background therapy, delivery route to parenteral All events will be adjudicated by a blinded, independent committee of clinical experts.;Timepoint(s) of evaluation of this end point: The primary endpoint will be analyzed using a stratified log-rank test with randomization stratification factors as strata. The point estimate of the hazard ratio with 95% CI will be estimated by a Cox regression model stratified by the randomization factors. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Multicomponent improvement endpoint measured by the proportion of participants achieving all of the following at Week 24 relative to baseline: -Improvement in 6MWD (increase = 30 meters [m]) -Improvement in NT-proBNP (decrease in NT-proBNP = 30%) or maintenance/achievement of NT-proBNP level < 300 ng/L -Improvement in WHO FC or maintenance of WHO FC II 2. Proportion of participants who maintain or achieve a low-risk category of REVEAL Lite 2 risk score at Week 24 versus baseline 3. Proportion of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French Risk score calculator 4. Change from baseline in NT-proBNP levels at Week 24 5. Proportion of participants who improve in WHO FC or maintain WHO FC II at 24 weeks from baseline 6. Change from baseline in 6MWD at Week 24 7. Change from baseline in the Physical Impacts domain score of Pulmonary Arterial Hypertension-Symptoms and Impact (PAH SYMPACT®) at Week 24 8. Change from baseline in the Cardiopulmonary Symptoms domain score of PAH-SYMPACT® at Week 24 9. Change from baseline in the Cognitive/Emotional Impacts domain score of PAH-SYMPACT® at Week 24;Timepoint(s) of evaluation of this end point: week 24 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czechia, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactMichela Brambatti
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Outcome results
None listed